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Understanding the brain requires studying its multiscale interactions from molecules to networks. The increasing availability of large-scale datasets detailing brain circuit composition, connectivity, and activity is transforming neuroscience. However, integrating and interpreting this data remains challenging. Concurrently, advances in supercomputing and sophisticated modeling tools now enable the development of highly detailed, large-scale biophysical circuit models. These mechanistic multiscale models offer a method to systematically integrate experimental data, facilitating investigations into brain structure, function, and disease. This review, based on a Society for Neuroscience 2024 MiniSymposium, aims to disseminate recent advances in large-scale mechanistic modeling to the broader community. It highlights (1) examples of current models for various brain regions developed through experimental data integration; (2) their predictive capabilities regarding cellular and circuit mechanisms underlying experimental recordings (e.g., membrane voltage, spikes, local-field potential, electroencephalography/magnetoencephalography) and brain function; and (3) their use in simulating biomarkers for brain diseases like epilepsy, depression, schizophrenia, and Parkinson's, aiding in understanding their biophysical underpinnings and developing novel treatments. The review showcases state-of-the-art models covering hippocampus, somatosensory, visual, motor, auditory cortical, and thalamic circuits across species. These models predict neural activity at multiple scales and provide insights into the biophysical mechanisms underlying sensation, motor behavior, brain signals, neural coding, disease, pharmacological interventions, and neural stimulation. Collaboration with experimental neuroscientists and clinicians is essential for the development and validation of these models, particularly as datasets grow. Hence, this review aims to foster interest in detailed brain circuit models, leading to cross-disciplinary collaborations that accelerate brain research.
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This content will become publicly available on December 4, 2025
Multiscale effective connectivity analysis of brain activity using neural ordinary differential equations
Neural mechanisms and underlying directionality of signaling among brain regions depend on neural dynamics spanning multiple spatiotemporal scales of population activity. Despite recent advances in multimodal measurements of brain activity, there is no broadly accepted multiscale dynamical models for the collective activity represented in neural signals. Here we introduce a neurobiological-driven deep learning model, termedmultiscale neuraldynamicsneuralordinarydifferentialequation (msDyNODE), to describe multiscale brain communications governing cognition and behavior. We demonstrate that msDyNODE successfully captures multiscale activity using both simulations and electrophysiological experiments. The msDyNODE-derived causal interactions between recording locations and scales not only aligned well with the abstraction of the hierarchical neuroanatomy of the mammalian central nervous system but also exhibited behavioral dependences. This work offers a new approach for mechanistic multiscale studies of neural processes.
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- PAR ID:
- 10590324
- Editor(s):
- Čanađija, Marko
- Publisher / Repository:
- PLOS
- Date Published:
- Journal Name:
- PLOS ONE
- Volume:
- 19
- Issue:
- 12
- ISSN:
- 1932-6203
- Page Range / eLocation ID:
- e0314268
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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